SBIR Direct Phase II Application Development of two simple and robust point-of-care assays for detection and therapy monitoring of hepatitis B in resource-limited settings Project Summary/Abstract Diagnostics for the Real World, Ltd (DRW) aims to develop and evaluate two point-of-care (POC) nucleic acid amplification tests (NAAT) for Hepatitis B virus (HBV): 1) HBV qualitative detection at a high sensitivity and 2) HBV semi-quantitative detection above or below a clinically significant cut-off for monitoring antiviral therapy (AVT). The test will be useful primarily in Sub-Saharan Africa (SSA) and other developing countries where HBV has a high prevalence and often exists as co-infection with Human Immunodeficiency virus (HIV-1). The tests will be developed and based on DRW?s existing SAMBA system, which was designed to allow NAAT use in POC settings in developing countries, by minimally trained staff and without the need for expensive equipment or temperature controlled transport and storage. DRW has SAMBA HIV-1 Qualitative and Semi-quantitative tests on the market with the latter in use in Malawi and Uganda by Mdecins Sans Frontires (MSF), where over 55,000 samples have been run on SAMBA in rural areas. The development of the HBV qualitative test will be based on the SAMBA HIV-1 Qualitative test. The HBV semi-quantitative test will be developed based on the SAMBA HIV-1 Semi-quantitative test, but with a cutoff of 20,000 IU/ml, recommended internationally for indication of AVT for chronic Hepatitis B (CHB) and for monitoring of therapeutic efficacy, rather than the 1,000 IU/ml cutoff used for HIV-1 treatment efficacy monitoring. Preliminary evaluation on panels covering all HBV genotypes and a range of HBV viral loads in left over clinical samples will be conducted in-house. The tests will then be evaluated in Ghana and Zimbabwe, examples of environments where the tests are intended for use and where HBV prevalence is high. After evaluations, DRW will submit the tests for WHO prequalification, CE marking and in-country approvals in Africa. Use of the SAMBA HBV tests will allow diagnosis and AVT monitoring of HBV infections in lower-level remote health care settings. In addition to allowing therapy for more patients, it will reduce the massive loss to follow-up (LTFU) experienced in SSA with HIV Anti-retroviral therapy (ART). It will also be a way of addressing the neglected health impact of chronic hepatitis B (CHB) at an early stage to prevent frequently fatal cirrhosis and hepatocellular carcinoma. WHO has stated in their document WHA67.6 that hepatitis is a significant health care issue that needs to be addresses in the same way that HIV-1 is being addressed and recommends provisions be made to diagnose, treat and monitor hepatitis, especially in the developing world, which does not have the same access to care as the developed world. The SAMBA HBV tests proposed in this application will support these WHO recommendations.